The invention relates to the treatment of hematologic disorders, e.g., disorders characterized by unwanted cells of hematopoietic origin, e.g., hematologic cancers.
Bone marrow transplantation (BMT) has yet to realize its full potential for the treatment of hematologic malignancies. A major obstacle to further advancement is graft-versus-host disease (GVHD), which has been prevented by removing T cells from the donor marrow. Unfortunately, T cell depletion has been associated with increased rates of engraftment failure and leukemic relapse. Despite improvements in pharmacologic GVHD prophylaxis, severe acute and chronic GVHD are still major complications of HLA-matched sibling bone marrow transplantation. Immunosuppressive drugs used for GVHD prophylaxis may also increase the relapse rate for certain types of leukemia. The patients receiving allogeneic BMT are, nevertheless, a fortunate select group: most patients do not have an HLA-matched sibling or a phenotypically matched unrelated donor, and therefore do not have the option of BMT. Attempts to perform BMT between strongly HLA-mismatched donor-recipient pairs have been associated with a prohibitively high incidence of severe GVHD and of failure of engraftment. Furthermore, a large fraction of leukemias and lymphomas afflict older patients who are more prone to the development of GVHD than are younger persons, and who therefore are not generally considered candidates for BMT, despite the lack of other curative options.